Silencing of RND3/RHOE inhibits the growth of human hepatocellular carcinoma and is associated with reversible senescence

BASBOUS, Sara; PAYSAN, Lisa; SENA, Sandra; ALLAIN, Nathalie; HIRIART, Jean-Baptiste; DUGOT-SENANT, Nathalie; ROUSSEAU, Benoît; CHEVRET, Edith; LAGREE, Valerie; MOREAU, Violaine

doi:10.1038/s41417-022-00445-6

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BASBOUS, Sara
BoRdeaux Institute in onCology [Inserm U1312 - BRIC]

PAYSAN, Lisa
BoRdeaux Institute in onCology [Inserm U1312 - BRIC]

SENA, Sandra
BoRdeaux Institute in onCology [Inserm U1312 - BRIC]

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Ce document a été publié dans

Cancer Gene Therapy. 2022-05-01, vol. 29, n° 5, p. 437-444

Résumé en anglais

Rnd3/RhoE is an atypical Rho GTPase family member, known to be deregulated in many types of cancer. Previously, we showed that RND3 expression is downregulated in hepatocellular carcinoma (HCC) cell lines and tissues. In cancer cells, Rnd3 is involved in the regulation of cell proliferation and cell invasion. The implication of Rnd3 in HCC invasion was importantly studied whereas its role in cell growth needs further investigation. Thus, in this work, we aimed to better understand the impact of Rnd3 on tumor hepatocyte proliferation. Our results indicate that the silencing of RND3 induces a cell growth arrest both in vitro in 2D and 3D culture conditions and in vivo in tumor xenografts. The growth alteration after RND3 silencing in HCC cells is not due to an increase of cell death but to the induction of senescence. This RND3 knockdown-mediated phenomenon is dependent on the decrease of hTERT expression. Interestingly, after re-expression of RND3, these cells are able to bypass senescence and regain the ability to proliferate, with a re-expression of hTERT. Given that a low expression of Rnd3 is linked to the presence of satellite nodules in HCC, the transient senescence state observed might play a role in cancer progression.< Réduire

Mots clés en anglais

Carcinoma

Hepatocellular

Cell Line

Tumor

Cell Proliferation

Humans

Liver Neoplasms

rho GTP-Binding Proteins

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